GHRP's (GHRP-2, hexarelin, peptidomimetic growth hormone secretagogue-GHS) administered chronically to short stature children with various degrees of GH deficiency or to obese subjects have produced anabolic effects by increasing the rate of body growth in children and increasing fat-free mass as determined by analysis of body composition with dual photon x-ray absorptometry (DEXA). These results were analogous to and predicted from results obtained from chronic administration of rhGH to elderly subjects. Furthermore, when rhGH was administered chronically to abdominally obese men, the abdominal fat mass decreased and lipoprotein and glucose metabolism improved. In addition, diastolic blood pressure was reduced. The route of administration of rhGH, daily injections or continuous infusion, also influenced the results in that rhGH administered continuously to GH deficient adults induced a greater reduction in total body fat than sc injections. A positive relationship between cortisol secretion and fat distribution in obese (especially visceral obesity) premenopausal women has been described. GHRPs in certain dosages and by specific routes of administration slightly and transiently raise serum cortisol levels. Also, GHRP may transiently impair glucose homeostasis which over time becomes negligible possibly because lean body mass is increased. The latter may represent increased skeletal muscle and perhaps an added route for glucose disposal. In reference to pulsatile GH secretion, the studies by Veldhuis et al indicate a dual defect in GH secretion and clearance in GH deficient adults. Also, these investigators have defined the differential impacts of age, sex steroid hormones and obesity on basal versus pulsatile GH secretion. Hartman et al demonstrated that low euglycemic dosages of recombinant IGF-I rapidly suppressed the fasting enhanced pulsatile release of GH. The objective of this study will be to determine the 24 hour pulsatile growth hormone levels and the IGF-1/IGFBP-3 levels after a 30 day chronic infusion of GHRP-2 to normal older men and women with decreased secretion of GH. In addition, effects on the following parameters will be studies: 1) body composition; 2) thyroid; 3) adrenal function; 4) serum PRL, cortisol; 5) serum lipoproteins; 6) glucose-insulin levels after an oral glucose tolerance test; 7) PTH; 8) osteocalcin; 9) C-terminal collagen propeptide (Prolagen-C); 10) Leptin.
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